Evaluating the utility of fluorine-18 fluorodeoxyglucose (<sup>18</sup>F-FDG)-positron emission tomography (PET)/ computed tomography (CT) scan in cancer of unknown primary.
Authors: Tharani Sivakumaran, Anthony Cardin, Jason Callahan, Hui-Li Wong, Richard Tothill, Rodney Hicks, Linda R. Mileshkin
Journal: Journal of Clinical Oncology (2022)

3062 Background: Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic tumours where standardized diagnostic work-up fails to identify the tissue of origin (TOO). Small studies, to date mainly focused on cervical lymph node squamous cell CUP patients, have shown 18 F-FDG-PET/CT can change patient management and identify the TOO. We aimed to describe the Peter MacCallum Cancer Centre experience with 18 F-FDG PET/CT in CUP with respect to detection of a TOO and its impact on management. A secondary aim was to compare the overall survival (OS) in patients where TOO is detected with those without TOO detection. Methods: Retrospective analysis of CUP patients treated between 2014-2020. Patients were identified from medical oncology clinics and PET/CT records. Information regarding demographics, clinicopathological details, CUP subtype as per ESMO guidelines, genomic analysis (If known), suspected TOO as per clinician pre- and post-FDG PET/CT, treatment details pre- and post FDG PET/CT and follow-up were collated from electronic medical records. Clinical details and genomic analysis were used to determine the clinically suspected TOO and compared against independent blinded nuclear medicine specialist FDG-PET/CT reads to determine sensitivity, specificity, accuracy and detection rate of TOO. Results: One hundred and forty-seven patients were identified of whom 65% had undergone molecular profiling. The median age at diagnosis was 61 years (range 20-84) and the median follow-up time was 69 months (range, 26–83). The predominant histological subtype was adenocarcinoma (54%). Eighteen percent of patients had a prior cancer history and 29% had a 1 st degree relative with a history of cancer. Ninety-three percent were ECOG 0-1, and the dominant metastatic site was lymph nodes (35%). Eighty-one percent were classified as unfavourable CUP subtype as per ESMO guidelines. FDG PET/CT demonstrated a TOO detection rate of 34% with high specificity (98%) and moderate accuracy (78%). FDG PET/CT resulted in a change in management in 22% of patients and identified occult disease sites in 37% of patients. The median OS for all patients was 17.8 months. Median OS was not reached and 12.5 months for favourable and unfavourable CUP subtypes, respectively (p &lt; 0.0001). Median OS when a potential TOO was identified on an FDG-PET/CT scan was 25.4 months compared with 9.1 months when a TOO remained elusive. (p &lt; 0.0001). Multivariable analysis of survival adjusted for age and sex remained significant for FDG-PET identification of TOO (p = 0.004), favourable CUP (p &lt; 0.001) and ECOG ≤ 1 (p &lt; 0.001). Conclusions: 18 F-FDG PET/CT plays a complementary role in CUP diagnostic work-up and was able to determine the likely TOO in a third of cases. OS is improved with TOO identification, demonstrating the value of access to a diagnostic PET/CT scan for CUP patients.